Integrative multiscale model of cardiac muscle contraction using protein elastic network.

Abstract

Although several computational models were proposed to simulate the cardiac sarcomere contraction process. Unfortunately, many of these models lack mechanistic details of how to incorporate mutation effects in the myofilament activation and predict how mutations can trigger cardiac diseases. In this study, an integrative multi-scale modeling approach that links atomistic molecular simulations of protein-protein interactions to the cellular level is proposed. More specifically, we propose to use an elastic network modeling method to solve for the small scale oscillations of tropomyosin dynamics on the actin surface and Langevin dynamics simulations based on stochastic theory to capture large scale oscillations. The proposed approach provides a more detailed molecular connection between tropomyosin dynamics and the generated force by the sarcomere. The methodology is flexible enough to include the effects of mutations on twitch dynamics without having to perform molecular dynamics simulation.